Androgens and estrogens rapidly facilitate short-term memory in the dorsal hippocampus of male mice.

Sex steroid hormones influence cognition through both classical delayed genomic and rapid mechanisms. While rapid estrogenic modulation of memory in the dorsal hippocampus (dHPC) is well established in females, the extent to which the sex hormones rapidly regulate short-term memory (STM) in males remains unresolved. Here, we investigated the rapid effects of the testosterone metabolites 17β-estradiol (E2) and dihydrotestosterone (DHT) on hippocampal-mediated STM in castrated CD1 male mice. Bilateral infusions into the dHPC were administered prior to testing object placement, object recognition, and social recognition STM, all completed within 40 min of treatment to capture rapid effects. Both E2 and DHT rapidly facilitated performance across paradigms, demonstrating that androgenic and estrogenic signaling within the male dHPC rapidly facilitates social and non-social STM processes. These findings extend the limited literature on sex steroid regulation of male cognition and underscore the importance of considering both estrogenic and androgenic pathways in models of hippocampal memory processing, with potential implications for understanding sex-specific vulnerabilities to cognitive decline and neuropsychiatric disorders.